Kirk Sorensen wrote:Quite feasible. Molybdenum forms a volatile hexafluoride (MoF6) which makes it straightforward to remove by fluorination, followed by fractional distillation to separate it from other hexafluorides.

I'm going to disagree with you on the feasibility portion.

It is true that Mo-99 has a fairly high fission yield, but it also has a very short half-life, less than 3 days, meaning that at equilibrium, concentrations are going to be very low.

The left handed side of the fission hump in all of the big three nuclides, U-233, U-235 and Pu-239 moves somewhat - in contrast to the right handed hump, but all contain significant amounts of Mo, specifically Mo-96, Mo-97, and Mo-98, all stable. This is going to make any Mo obtained be highly contaminated with stable isotopes.

The fractional distillation of anything is going to involve some impurities, ever the more so in a situation where the distillates are in a radiation field.

Moreover one needs not only to purify it, but also reduce it and, potentially reoxidize it to make it available for fast ion exchange (or other ion chromatography.)

Tc-99, the long lived isomer of Tc-99m, is also very volatile and it will necessarily contaminate to some extent any distilled Mo. Although present as a trace impurity, this may still overwhelm Tc-99m, which will also be in equilbrium with Mo-99, and will have a low concentration because of its even shorter half-life.

Effectively, since radiochemical complexing agents are often expensive molecules in their own right, one is going to almost insist on high radiochemical isotopic purity.

I'm going to guess that Tc-99m will almost always be made in accelerators.

Actually, most Tc-99m from Mo-99 which is made in a reactor and is extracted as a fission product. They usually have a target of highly enriched uranium which they reprocess to extract the molybdenum. This is made into a Tc-99m generator which is shipped to the hospital which extracts the Tc-99m. See http://en.wikipedia.org/wiki/Technetium-99m_generator. It is an issue recently because the Canadian reactor which produces a significant amount of the world's supply is down, and the two Maple reactors that they were going to replace it didn't work.

It is made with an enriched uranium target in a reactor which is reprocessed just for this. It is highly inefficient because one needs a whole reactor just to irradiate this target, and most of the molybdenum is in the non-reprocessed part of the reactor. In an MSR, the entire inventory of fission products are available in liquid form.

Short life of an isotope
A "For Rent" sign stands in front of a nondescript building in Dorval's industrial park, giving no hint of the life-saving work going on inside.
By Aaron Derfel, The Gazette, July 4, 2009

The building's windows are tinted and the front door is locked. Yet behind the walls, Geiger counters are crackling as technicians prepare doses of radioactive medical isotopes to help doctors diagnose cancer and heart disease.

The radiopharmacy runs seven days a week, 24 hours a day, supplying most of Montreal's hospitals, but its owners want to keep the location a secret.

"We don't want any publicity," said Cyrille Villeneuve, vice-president (international) of Lantheus Medical Imaging. "You know, there are activists and we have radioactive materials." A single dose of medical isotopes is no more radioactive than a chest X-ray. But the technicians at the Dorval radiopharmacy handle generators buzzing with isotopes that are hundreds of times more radioactive than what is in injected into a patient's arm.

Still, "it's not something to be scared of - working with radiation," said Sacha Des Serres, a technician with a meticulous manner and an easy smile.

"We're well protected," she added, showing off a dosemeter ring, which measures her potential radiation exposure. "We stand behind lead shields and everybody works well together." Unlike the corner pharmacy, the Lantheus facility does not stock drugs with long-term expiry dates. Medical isotopes, which course through the body as tracers to diagnose disease and to treat some forms of cancer, cannot be stockpiled. You can't see these isotopes with your own eyes, smell them or taste them because they're nothing more than a small collection of radioactive atoms.

Their sole purpose is to emit gamma rays from internal organs for scanning by medical-imaging cameras.

As if they weren't elusive enough, the most common isotope employed in nuclear medicine - technetium-99m - has a half-life of only six hours. Derived from the Greek word "technikos," meaning "artificial," technetium-99m doesn't even exist in nature. It's forged partly in a nuclear reactor, and after six hours, half of a dose disappears, and after another six hours, half of what remains vanishes as well, and so on.

Therefore, time is of the essence when dealing with medical isotopes, and that's why a radiopharmacy operates 24 hours a day. But since the end of May, when Ontario's aging Chalk River nuclear reactor shut down because of a leak, isotopes have been in short supply across North America.

Quebec hospitals have put off at least 12,000 diagnostic tests and have delayed the treatment of some patients with thyroid cancers. The Dorval radiopharmacy has resorted to ordering isotopes that are manufactured by nuclear reactors in Europe and South Africa.

By plane and by truck, the isotopes arrive at the Dorval facility each day in boxes marked with the stark tri-blade radiation symbol. Inside those boxes sit 300-pound, lead-encased isotope generators, or cows, as the technicians prefer to call them. To the untrained eye, a generator could be mistaken for a milk bucket.

In the unseen core of each generator is a pencil-sized column of alumina powder. It's the alumina that absorbs the isotopes - in this case, molybdenum-99. Moly-99 is what is actually created in the nuclear reactor. It has a half-life of 66 hours, making the isotope ideal at this stage for transport in trans-Atlantic flights to radiopharmacies.

As Moly-99 decays inside the generator, it gives birth to a daughter - yes, daughter is the word nuclear physicists use - named technetium-99m, or Tc-99m for short. The generator is good for a week before it runs out of most of its isotopes.

So what Des Serres and her colleagues do is "milk" the "moly cow" for technetium. Actually, the process is quite delicate: It involves infusing a saline solution into the column in the generator and rinsing Tc-99m from the alumina. The isotope, in a clear liquid, is milked out of the top of the generator into a vacuum-pressurized vial.

Since Moly-99 is not soluble, it stays behind in the generator, continuously decaying into technetium.

Usually, a technetium generator is milked once or twice a day. But given that the Chalk River reactor is down and had met more than 30 per cent of the world's isotope needs, radiopharmacy technicians are now milking their moly cows up to four times daily. This poses a problem, because the technicians must also squeeze in the time to prepare doses in syringes.

What's more, quality-control technicians have to double-check the technetium for impurities right after it's milked from the moly cow as well as the doses before they are shipped to hospitals.

"It's more trouble," said Richard Dubois, manager of the Dorval radiopharmacy.

"We're doing the best we can but we're limited by the amount of raw material we get. As a result, we have to work much harder just to produce the same number of doses."

Standing behind a lead shield, Des Serres started to fill an isotope prescription for a patient who was only known to her as a bar code on a label. She peered through a thick lead glass window as she stuck the needle of a syringe into the top of a vial in a lead container, slowly drawing out the technetium. The Geiger counters clicked in the background; if they suddenly screeched, that would have signaled a major radiation leak.

Depending on the purpose of the dose - whether to study heart function or to determine whether a cancer has spread to the bone - the technetium is "tagged" to a chemical compound. The syringes are then encapsulated in colour-coded lead tubes, and placed inside virtually indestructible lead suitcase. Drivers waiting outside transport the suitcases in unmarked vans to hospitals. To make sure the patient receives enough of a dose, Des Serres will boost the amount of initial radiation in the syringe to take into account transport time and technetium's short half-life.

"If we can free up the hospitals by making these doses, that's a good thing," she said.

Ironically, the one hospital in Montreal that doesn't receive doses from a radiopharmacy is not suffering from a lack of isotopes. In fact, Jean Talon Hospital is sending some of its excess isotopes to other local hospitals.

Years ago, Jean Talon signed a contract with a U.S. supplier for weekly shipments of technetium generators. Each weekday at the community hospital in Villeray, a technician milks the generator and readies the doses.

"Since we do everything at our hospital, there is no loss of isotopes," explained André Arsenault, Jean Talon's chief of nuclear medicine. "When the isotopes are prepared at a radiopharmacy at 5 a.m., by the time they arrive at our hospital, half the doses are gone because of their short half-life."

This is not to suggest that the isotope shortage could be resolved if every hospital was furnished with its own generators. The crisis came about in the first place because of Chalk River's breakdown, not because of any problems in the distribution network. And Jean Talon, unlike some of the big teaching hospitals, doesn't have a huge volume of patients.

But the pony-tailed Arsenault, who has a strong independent streak and likes to keep a close watch on things in his department, prefers to have a technetium generator on site.

On a rainy June morning, Arsenault was reviewing the medical file of a patient, 73-year-old Aimé Brunelle, who was about to undergo an isotope diagnostic scan of his heart.

Two days earlier, a gamma camera scanned Brunelle's heart while he was at rest. And now Brunelle had returned to undergo a second scan during a stress test. Since Brunelle weighs more than 350 pounds, Arsenault decided against having him run on a treadmill.

A nurse injected him instead with Persantin to boost his heart rate. Brunelle lay on a stretcher, and after only a couple of minutes, his breathing grew laboured.

The nurse then injected him with Myoview, a cardiac imaging agent that is tagged with technetium. The agent zeroes in on the heart, with the isotopes tagging along for the ride.

Once the technetium reaches the heart, it emits gamma rays. Unlike an X-ray, which is beamed from a machine outside into the body, isotopes shoot rays from within organs like the heart.

X-rays take detailed images of fractured bones. MRI and PET scans reveal tumours swelling inside organs. By comparison, medical isotopes are used to analyze organ function and can even predict the onset of disease. And that's what makes them so indispensible to modern medicine.

A half hour later, Brunelle lay on a bed as it slid under a huge, multi-million-dollar gamma camera. The machine took 20-second images of his heart from different angles, a computer recreating a 3-D image of the organ.

Later that morning in his office, Arsenault called up the images of Brunelle's heart on his computer screen.

"For a big man, he has a small heart," Arseneault said, studying the "before" and "after" pictures.

He clicked on his mouse, calling up a 3-D computerized animation of Brunelle's heart beating. This time, the "before" and "after" images were much easier for the layman to understand, highlighting in orange and red the heart pumping blood.

"His heart's fine," Arsenault concluded. "There's not much difference between the two images."

Brunelle, a jovial snow-removal operator with 50 years' experience, had already left the hospital. He would receive some good news later that day - thanks, in part, to a daughter named technetium-99m.

- - -

From Reactor to Hospital

Swords into ploughshares: some of the highly enriched uranium from decommissioned U.S. nuclear warheads is sent to Chalk River to make medical isotopes.

Chalk River's National Research Universal reactor was shut down for a three-month repair at the end of May, and is to be phased out by 2016. For the purposes of this graphic, Chalk River is used as an example.

A uranium-aluminum alloy no bigger than a highlighter marker is fixed as a target in the nuclear reactor. It's bombarded with neutrons for five to seven days. Through fission, radioactive molybdenum-99 is created, along with other isotopes.

The irradiated target is cooled for a half a day, and undergoes first-stage processing at Chalk River. In liquid form, it's transported in a shielded cask to a "hot cell" at the nearby MDS Nordion facility for final processing for up to 19 hours. Workers operating remote manipulators treat the target with chemicals to recover pure Moly-99.

The Moly-99 is sent by plane to a plant in Billerica, close to Boston, to be incorporated into lead-shielded isotope generators.

The generators are shipped to radiopharmacies and some hospitals across Canada and the U.S. Technicians extract from the generators the daughter radioisotope of Moly-99, technetium-99m.

Time is critical because of the short halflife of Moly-99: Less than 24 hours elapse from the moment it's purified at MDS Nordium until a technetium generator is made in Billerica.

About 97 per cent of the highly enriched uranium that is used in making medical isotopes ends up as waste that must be stored. It has a half-life of 700 million years.

I read that there are 20 million procedures done with Tc-99m a year in the US. I don't know what it costs, but a wild guess would be $100 per dose, or 2 billion a year for the US. I think 4 millicurie is a typical amount used, or 80,000 curies a year. Is this a big enough market to get a MSR built? Could it be built with less regulation if it did not generate electricity and was built in a remote place? Or are those days gone forever?

The proposed isotope production facility would make Mo-99 and other fusion isotopes in an aqueous homogeneous reactor (AHR), also known as a solution reactor. This reactor uses low-enriched uranium (LEU) for both fuel and target, rather than the high-enriched uranium (HEU) now used in producing medical isotopes, addressing the concerns that last month prompted the National Academy of Sciences to issue a report urging medical isotope providers to switch from HEU to LEU to produce medical isotopes.

"It is self-limiting, which is an inherent safety feature," Reynolds said. Also, each AHR produces only about 200 kilowatts of power, while a research reactor produces about 45 thousand kilowatts (45 megawatts) and power reactors produce about a thousand megawatts. "Each of these reactors is in the neighborhood of 2 feet in diameter and 4 feet tall and works at atmospheric pressure. It also operates at 80 degrees centigrade, so there are no high temperatures to worry about."

It will be nice to at least have a liquid fuel reactor operating somewhere in the world even if it is not molten salt.